他汀类药物减轻接受蒽环类药物和/或曲妥珠单抗治疗的癌症患者心脏毒性的效果：系统评价和荟萃分析。
Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis.
机构信息
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Department of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA.
出版信息
Cancer Causes Control. 2021 Dec;32(12):1395-1405. doi: 10.1007/s10552-021-01487-1. Epub 2021 Aug 18.
PURPOSE
Cardiotoxicity affects 5-16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies.
METHODS
A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran's Q test and the I test.
RESULTS
Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27-0.78), p = 0.004, [Formula: see text] = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17-1.45), p = 0.20, [Formula: see text] = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75-9.52), p < 0.001, [Formula: see text] = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82-11.68, p = 0.024, [Formula: see text] = 80.9%]. We were unable to explore publication bias due to the small number of studies.
CONCLUSION
This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab.
TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION
PROSPERO: CRD42020140352 on 7/6/2020.
目的
蒽环类药物和/或曲妥珠单抗治疗的癌症患者中有 5-16%会发生心脏毒性。目前已有有限的研究探讨了减轻心脏毒性的干预措施。我们通过对已发表研究进行系统评价和荟萃分析，研究了他汀类药物在减轻心脏毒性方面的作用。
方法
使用 PubMed、Embase、Web of Science、ClinicalTrials.gov 和 Cochrane 中心进行文献检索。使用随机效应模型评估汇总相对风险（RR）、加权均数差（WMD）和相应的 95%置信区间。使用 Cochran's Q 检验和 I 检验检验研究之间的异质性。
结果
两项包含 117 例患者的随机对照试验（RCT）和四项包含 813 例患者的观察性队列研究纳入了分析。汇总结果表明，在队列研究中，他汀类药物使用者在接受蒽环类药物和/或曲妥珠单抗治疗后，心脏毒性明显减轻[RR=0.46，95%CI（0.27-0.78），p=0.004，[Formula: see text]=0.0%]，而在 RCT 中他汀类药物使用者心脏毒性风险无显著降低[RR=0.49，95%CI（0.17-1.45），p=0.20，[Formula: see text]=5.6%]。在队列研究中，与基线相比，他汀类药物使用者在接受蒽环类药物和/或曲妥珠单抗治疗后左心室射血分数显著升高[加权均数差（WMD）=6.14%，95%CI（2.75-9.52），p<0.001，[Formula: see text]=74.7%]，而在 RCT 中也有显著升高[WMD=6.25%，95%CI（0.82-11.68），p=0.024，[Formula: see text]=80.9%]。由于研究数量较少，我们无法探讨发表偏倚。
结论
本荟萃分析表明，他汀类药物的使用与蒽环类药物和/或曲妥珠单抗治疗后的心脏毒性风险降低之间存在关联。需要进行更大规模、设计良好的 RCT 来确定他汀类药物是否能降低蒽环类药物和/或曲妥珠单抗引起的心脏毒性风险。
临床试验注册号和注册日期
PROSPERO：CRD42020140352，于 2020 年 7 月 6 日注册。
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